A macrophage migration inhibitory factor polymorphism is associated with autoimmune hepatitis severity in US and Japanese patients
DN Assis, H Takahashi, L Leng, M Zeniya… - Digestive diseases and …, 2016 - Springer
DN Assis, H Takahashi, L Leng, M Zeniya, JL Boyer, R Bucala
Digestive diseases and sciences, 2016•SpringerBackground The pathogenesis of autoimmune hepatitis (AIH) is incompletely understood.
Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine implicated in the
pathophysiology of multiple autoimmune diseases. We recently reported that MIF expression
was increased in a US AIH cohort. MIF expression in non-Western AIH patients is unknown.
A MIF-173 GC single nucleotide polymorphism in the MIF promoter (rs755622) is clinically
associated with steroid resistance in several inflammatory disorders but has not been …
Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine implicated in the
pathophysiology of multiple autoimmune diseases. We recently reported that MIF expression
was increased in a US AIH cohort. MIF expression in non-Western AIH patients is unknown.
A MIF-173 GC single nucleotide polymorphism in the MIF promoter (rs755622) is clinically
associated with steroid resistance in several inflammatory disorders but has not been …
Background
The pathogenesis of autoimmune hepatitis (AIH) is incompletely understood. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine implicated in the pathophysiology of multiple autoimmune diseases. We recently reported that MIF expression was increased in a US AIH cohort. MIF expression in non-Western AIH patients is unknown. A MIF-173 GC single nucleotide polymorphism in the MIF promoter (rs755622) is clinically associated with steroid resistance in several inflammatory disorders but has not been evaluated in AIH.
Aim
To compare MIF polymorphisms and their relationship to clinical parameters in AIH patients from the USA and Japan.
Methods
DNA and matched sera from AIH patients and healthy controls from Japan (N = 52) were compared to the US group. Serum concentrations of MIF and its circulating receptor CD74 were measured by ELISA. MIF-173 GC (rs755622) and MIF-794 CATT5–8 (rs5844572) polymorphisms were analyzed by standard methods. MIF genotypes were correlated with serum ALT and steroid requirements.
Results
Serum MIF was increased in Japanese AIH patients versus local controls, in agreement with the US AIH patients. Within both AIH groups, ALT was higher in CC/GC versus GG patients. Further, the steroid requirement was higher in AIH patients with GC/CC genotypes from both groups. In the Japanese patient group, the GC/CC genotype also was associated with acute symptomatic presentation.
Conclusions
The MIF-173 CC/GC genotypes may be associated with both higher ALT and maintenance steroid requirements in AIH patients from the USA and Japan. This polymorphism could be a marker of disease severity in AIH patients.
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